Project Summary/Abstract Research in posttraumatic stress disorder (PTSD), more specifically in traumatized refugees, has primarily focused on adults. My Co-Sponsor (Dr. Javanbakht) has conducted the first mental health study of Arab refugees (adults and children) resettling in the United States that evaluates prevalence, genetic, epigenetic, and environmental correlates of trauma-related psychological outcomes. My Sponsor (Dr. Jovanovic) has pioneered longitudinal studies of trauma in youth, employing skin conductance response (SCR) and fear-potentiated startle (FPS) to understand physiological correlates of psychopathology. The goal of this application is to expand my Sponsors? work to quantify neurophysiological biomarkers of PTSD in youth refugees. Exposure to stress and trauma activates a key adaptive pathway?the sympathetic adrenomedullary system (SAM). Increased sympathetic reactivity is measurable through non-invasive methods. Skin conductance response (SCR) rises when recounting trauma and can predict PTSD 6 months following exposure. FPS quantifies impairments in safety learning as well as overgeneralization of fear. Elevated levels of pro- inflammatory components have been linked to more severe pathology of PTSD and anxiety. The proposed project will measure the relationship between PTSD and its symptom clusters, and SCR, FPS, and inflammation in Syrian refugee youth who have been exposed to civilian war trauma and have been assessed for possible anxiety disorder. This will provide the trainee with an opportunity to i) enhance skills engaging with multicultural populations in clinical research, ii) learn the FPS paradigm as well as how to analyze electromyography recordings (EMG; tool to measure startle response) and SCR, and iii) to enhance skills in collection, storage, and analysis of pro-inflammatory proteins, all while expanding the understanding of the neurophysiological basis of PTSD in youth, which has been grossly underexplored. Scientific premise: Biomarkers such as SCR, FPS, and inflammation (namely acute phase protein C-reactive protein (CRP)) will be quantifiable correlates of PTSD in Syrian refugee youth. Such biomarkers will be significantly elevated in those who have screened positive for an anxiety disorder compared to those who have not. Significance: Our approach will facilitate investigation of plausible neurobiological mechanisms associated with psychophysiopathology of PTSD in youth, providing data from a largely underrepresented group in mental health research?Middle Eastern refugees. Potential future research would: A) investigate volumetric and functional neuroimaging correlates of the behavioral, inflammatory, and electrophysiological changes associated with trauma in children and adolescents; B) leverage this information to build a predictive model combining baseline measures of inflammatory state, autonomic arousal, brain structure, and psychological symptoms in order to determine prognosis and progression in youth; and C) expand these methods of mechanistic inquiry for use in assessing body-focused treatment modalities and outcomes, particularly exercise and mindfulness-based interventions.